Project Summary This application is submitted in response to PA-15-039 (Diabetes and Cardiovascular Disease in Older Adults). Nutrition is important in the prevention and management of cardiometabolic diseases, including diabetes mellitus and cardiovascular diseases. Poor dietary patterns increase the risk of cardiometabolic diseases; on the other hand, healthy dietary patterns lower risk of cardiometabolic diseases and improve measures of cardiometabolic health (improved glycemic control and lipid metabolism, reductions in obesity and blood pressure). However, current dietary interventions to achieve these goals are not uniformly effective for all individuals. Identifying novel biomarkers of diet and cardiometabolic health could lead to a better understanding of how diet influences cardiometabolic health, and help design more effective dietary interventions and patient-centered strategies to prevent cardiometabolic diseases. The goal of this exploratory R03 study, led by a New Investigator, is to establish the feasibility of using monocyte transcriptomic and methylomic measures to identify potential biomarkers of diet and cardiometabolic health in older adults. We will leverage existing data from the Multi-Ethnic Study of Atherosclerosis (MESA) in 1,264 Exam 5 participants aged 55 ? 94 years (51% female, 46% Whites, 33% Hispanics, 21% Blacks). Measures include food frequency questionnaires, gene expression and DNA methylation data, and measures of cardiometabolic health. To evaluate diet quality, we will develop dietary indices from food frequency questionnaire responses to assess adherence to the 2010 Dietary Guidelines for Americans (HEI-2010 & AHEI-2010), the Dietary Approaches to Stop Hypertension (DASH) diet, and a Mediterranean-style (aMED) diet. We will investigate associations between dietary indices (and individual dietary index components) with cross-sectionally ascertained genome- wide measures of gene expression (transcriptome) and DNA methylation (methylome) in CD14+ purified monocytes. Molecular features associated with diet will be investigated for potential mediating effects on cardiometabolic-related traits (e.g. HbA1c, triglycerides, cholesterol, obesity, blood pressure). Promising findings will be replicated using existing data from an additional 936 MESA Exam 5 participants. We posit that the results will enable us to (a) establish the feasibility of utilizing monocyte transcriptomic and methylomic measures to identify potential biomarkers of diet and cardiometabolic health in older adults, and (b) estimate anticipated effect sizes and sample sizes necessary for future larger-scale studies.